With continued advances in strategies to detect cancer early and treat it effectively along with the aging of the population, the number of individuals living years beyond a cancer diagnosis can be expected to continue to increase. Although beneficial and often lifesaving against the diagnosed malignancy, most therapeutic modalities for cancer are associated with a spectrum of late complications ranging from minor and treatable to serious or, occasionally, potentially lethal. Taken as a whole, investigators conducting research among long-term cancer survivors (those 5 years or more beyond cancer diagnosis) are reporting that long-term adverse outcomes are more prevalent, serious, and persistent than expected in survivors of both pediatric and adult cancer. However, the long-term and late effects of cancer and its treatment remain poorly documented and understood among those diagnosed as adults. These data underscore the need for continued research in this ever-growing portion of the cancer survivorship spectrum. This article examines (1) definitional issues relevant to cancer survivorship, (2) the evolving paradigm of cancer survivorship research, (3) prevalence data for cancer survivors, (4) research needs and issues of particular relevance to long-term cancer survivors, and (5) cancer survivorship as a scientific research area with an overview of physiologic/medical sequelae of cancer diagnosis and treatment and the grading of late effects. A large and growing community of cancer survivors is one of the major achievements of cancer research over the past 3 decades. Both length and quality of survival are important endpoints. Many cancer survivors are at risk for and develop physiologic and psychosocial late and long-term effects of cancer treatment that may lead to premature mortality and morbidity. Interventions-therapeutic and lifestyle-may carry the potential to treat or ameliorate these late effects and must be developed, examined, and disseminated if found effective.